Overview

This trial is active, not recruiting.

Condition unspecified adult solid tumor, protocol specific
Treatment alvespimycin hydrochloride
Phase phase 1
Sponsor Institute of Cancer Research, United Kingdom
Collaborator National Cancer Institute (NCI)
Start date October 2005
End date January 2007
Trial size 35 participants
Trial identifier NCT00248521, CDR0000442402, ICR-PH1/102, NCI-6547

Summary

RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) at 28 days after treatment
time frame:

Secondary Outcomes

Measure
Heat shock protein 90 (HSP90) client protein and co-chaperone changes up to 29 days after treatment
time frame:
Tumor response by RECIST criteria every 6 weeks while on study
time frame:
Clinical pharmacokinetic profile established during the first course of treatment
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed solid tumor - Unresectable or metastatic disease - Standard curative or palliative measures do not exist OR are no longer effective OR patient refused such measures - No known brain metastases PATIENT CHARACTERISTICS: Age - 18 and over Performance status - ECOG 0-1 Life expectancy - More than 12 weeks Hematopoietic - Absolute neutrophil count > 1,500/mm^3 - Platelet count ≥ 100,000/mm^3 - Hemoglobin ≥ 9.0 g/dL Hepatic - Bilirubin normal - ALT and AST ≤ 1.5 times upper limit of normal - No chronic liver disease - Hepatitis B or C negative Renal - Creatinine normal OR - Creatinine clearance normal Cardiovascular - No symptomatic New York Heart Association class III-IV cardiac disease - No myocardial infarction within the past year - No active ischemic heart disease within the past year - No poorly controlled angina - No uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs - No transient ischemic attack - No stroke - No peripheral vascular disease - No congenital long QT syndrome - No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) - QTc < 450 msec (for men) and 470 msec (for woman) - LVEF > 40% by MUGA - No left bundle branch block Pulmonary - No symptomatic pulmonary disease requiring medication, including any of the following: - Dyspnea with or without exertion - Paroxysmal nocturnal dyspnea - Oxygen requirement - Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment - No known HIV positivity - No other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer - No ongoing or active infection - No diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers) - No psychiatric illness or social situation that would preclude study compliance - No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy - More than 4 weeks since prior immunotherapy - Concurrent epoetin alfa allowed Chemotherapy - More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) - No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) Endocrine therapy - More than 4 weeks since prior endocrine therapy - Concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed Radiotherapy - More than 4 weeks since prior radiotherapy (except for palliative treatment) - No prior irradiation field that potentially included the heart (e.g., mantle) Surgery - Not specified Other - Recovered from all prior therapy - Concurrent bisphosphonates allowed - At least 5 half-lives since prior and no concurrent medication that prolong QTc - No other concurrent anticancer or investigational agents - No concurrent grapefruit juice

Additional Information

Official title A Cancer Research UK Phase I Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of 17-Dimethylaminoethyl-amino-17-Demethoxygeldanamycin (17-DMAG) Given as a Once Weekly Infusion in Patients With Advanced Solid Tumors
Description OBJECTIVES: Primary - Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with unresectable or metastatic solid tumors. - Determine the feasibility, safety, and toxicity profile of this drug in these patients. Secondary - Determine the clinical pharmacokinetic profile of this drug in these patients. - Determine tumor response in patients treated with this drug. - Determine the biologically effective dose. OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study. Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD. After completion of study treatment, patients are followed for 28 days. PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study within 12-18 months.
Trial information was received from ClinicalTrials.gov and was last updated in August 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).